Disease Prevention- Cardiovascular disease
Interest in garlic and its potential to prevent cardiovascular disease began with observations that people living near the Mediterranean basin had lower mortality from cardiovascular disease. Garlic is a common ingredient in Mediterranean cuisine, but a number of characteristics of the “Mediterranean diet” have been proposed to explain its cardioprotective effects. Although few observational studies have examined associations between garlic consumption and cardiovascular disease risk, numerous intervention trials have explored the effects of garlic supplementation on cardiovascular disease risk factors.
Platelet aggregation is one of the first steps in the formation of blood clots that can occlude coronary or cerebral arteries, leading to myocardial infarction or ischemic stroke, respectively. Evidence that garlic inhibits platelet aggregation is based mainly on in vitro experiments and a small number of ex vivo assays. Of 10 randomized controlled trials that tested the antithrombotic effect of garlic preparation, four reported a modest but significant decrease in ex vivo platelet aggregation with garlic supplementation compared to placebo. Because garlic oil extract in particular may have antithrombotic activity, a small randomized controlled trial in 12 healthy adults was conducted to test the acute effect of one large dose of garlic oil (extracted from 9.9 g of fresh garlic) on ex vivo platelet aggregation. The garlic oil extract had a mild effect on adrenaline-induced platelet aggregation (12% reduction) but had no effect on adenosine diphosphate (ADP)- or collagen-induced aggregation measured four hours post-consumption. Another study in 14 healthy volunteers showed that aged garlic extract dose-dependently inhibited ADP-stimulated platelet aggregation by downregulating the fibrinogen binding activity of glycoprotein IIb/IIIa fibrinogen receptor found on platelets.
Serum lipid profiles
A recent systematic review of randomized controlled trials examining the effect of supplementation with various garlic preparations on serum lipid profiles in individuals with elevated and normal serum cholesterol levels reported mixed results. The most recent and comprehensive meta-analysis compared the results from 39 randomized controlled trials published between 1955 and 2011 that tested the effect of garlic preparations on serum lipid concentrations. These 39 trials studied 2,298 adult participants (mean age, 49.5 years), administered garlic-only preparations, used a true placebo, and lasted for at least two weeks. The majority of included trials recruited subjects with elevated total cholesterol at baseline (>200 mg/dL [>5.2 mmol/L], 29 trials) and lasted more than eight weeks (30 trials). The authors found that garlic preparations significantly lowered total cholesterol and low-density lipoprotein (LDL)-cholesterol compared to placebo. High-density lipoprotein (HDL)-cholesterol concentrations were mildly increased and triglyceride concentrations were not affected by garlic supplementation. All administered garlic preparations (garlic powder, aged garlic extract, garlic oil, and fresh garlic) were well tolerated and associated with only minor side effects (garlic odor and mild gastrointestinal discomfort).
Although garlic supplementation for a minimum of two months may lower total- and LDL-cholesterol concentrations in individuals with elevated total cholesterol, the benefits may not last beyond the short term . Whether garlic possesses long-lasting lipid-lowering effects remain questionable and future investigations may focus on ways to maximize potential benefits of garlic preparations on serum lipids.
Very few studies have attempted to assess the effect of garlic supplementation on the progression of atherosclerosis in humans. One early study in Germany used ultrasound imaging to assess the effect of 900 mg/day of dehydrated garlic on the progression of atherosclerotic plaque in the carotid and femoral arteries. After four years, the increase in plaque volume was significantly greater in women taking the placebo (+53.1%) than in women taking the garlic supplement (-4.6%), while no significant difference in plaque volume was found between garlic (+1.1%) and placebo (+5.5%) in men. In a smaller pilot study, investigators measured coronary artery calcium using electron-beam computed tomography to assess the effect of supplementation with aged garlic extract on the progression of atherosclerosis in 19 adults already taking HMG-CoA reductase inhibitors (lipid-lowering drugs also known as statins).After one year, increases in coronary artery calcium score were significantly lower in those taking aged garlic extract than in those taking a placebo. Nevertheless, although coronary calcium scores may have a predictive value regarding future cardiac events in asymptomatic subjects, it may not be a reliable marker of plaque burden in symptomatic patients. In a recent double-blind, controlled study, the extent of coronary atherosclerosis was assessed with cardiac computed tomography angiography in 72 individuals (55 at study completion) at high risk of coronary heart disease randomized to receive either 2,400 mg of aged garlic extract or placebo for 52 weeks. The result suggested a significant decrease in the extent of coronary plaques with low-attenuation area (a type of vulnerable plaques prone to rupture).with aged garlic extract compared to placebo, but no differences in total plaque volume and proportions of non-calcified plaques and dense calcium were found between treatment and placebo groups.
Most systematic reviews and/or meta-analyses of randomized controlled trials to date have provided mixed results regarding the potential blood pressure-lowering effect of garlic, possibly because most of these trials enrolled both normotensive and hypertensive subjects.
A systematic review and meta-analysis by Xiong et al. included seven randomized, placebo-controlled trials that exclusively enrolled individuals with high blood pressure, i.e., with systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg. Five out of seven trials identified in this systematic review reported statistically significant reductions in SBP and DBP with several garlic preparations (dried garlic homogenate, garlic powder, and aged garlic extract). Another recent meta-analysis included nine randomized controlled trials in 482 hypertensive individuals who were given garlic powder (six studies), garlic homogenate (one study), aged garlic extract (two studies), or placebo for 8 to 26 weeks. Garlic preparations were found to significantly reduce SBP by a mean of 9.1 mm Hg and DBP by a mean of 3.8 mm Hg compared to placebo. The most recent meta-analysis found that garlic preparations reduced SBP by a mean 8.7 mm Hg (10 trials, 440 subjects) and DBP by 6.1 mm Hg (8 trials, 257 subjects). Such reductions in blood pressure seem comparable to those reported with currently used classes of blood pressure-lowering medications (average reduction, -9.1 mm Hg for SBP and -5.5 mm Hg for DBP). The effect of blood pressure reduction from such medications at standard dose has been estimated to lower the risk of coronary heart disease events by about one-quarter and the risk of strokeby about one-third. Nonetheless, evidence showing that garlic supplements may reduce the risk of cardiovascular morbidity and mortality is still lacking.
In a recent 12-week, randomized, placebo-controlled trial in untreated hypertensive subjects, daily intake of aged garlic extract (1.2 g of which contained 1.2 mg of S-allyl-L-cysteine [SAC]) was shown to significantly lower SBP by 11 mm Hg and DBP by 6 mm Hg on average in 50%-60% of participants, but reductions in blood pressure were not reported in 40%-50% of participants compared to placebo. Whether interindividual differences in nutritional status and genetic polymorphisms can explain differences in blood pressure response to garlic treatment need to be explored in future studies.
Overall, short-term garlic supplementation appears to effectively reduce blood pressure with minimal side effects in hypertensive patients.
The results of randomized controlled trials have suggested that garlic supplementation modestly improves serumlipid profiles in individuals with elevated serum cholesterol and reduces blood pressure in hypertensive subjects. It is not yet clear whether garlic supplementation can reduce atherosclerosis or prevent cardiovascular events, such as myocardial infarction or stroke.